JPH11130602A - Use of composition for controlling hazardous microorganism excellent in safety to living body for disinfection and preservation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide the use of a hazardous microorganism-controlling composition having high safety to living bodies for disinfection and preservation. SOLUTION: This hazardous microorganism-controlling composition comprises (A) a surfactant, (B) a nonreducing saccharide or polyol and (C) a chelating agent and is used for disinfection and/or preservation. In this composition, the surfactant is at least one selected from the group consisting of cationic, anionic, amphoteric and nonionic compounds; the nonreducing saccharide is a 1-O-alkylglucose, sucrose, trehalose, mannitol, maltitol, xylitol or erythritol and the like; and the nonreducing polyol is ethylene glycol, glycerol, propylene glycol, polyvinyl alcohol or polyethylene glycol.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to the use of a composition for controlling harmful microorganisms for disinfection and preservation. More specifically, the composition can be used as a preservative and a disinfectant for cleaning and preserving solutions for contact lenses, a preservative and a disinfectant for various pharmaceutical preparations, quasi-drugs, and cosmetics, including eye drops and dental agents. Related to the use as an agent.

[0002]

2. Description of the Related Art In industry, development of antibacterial agents, disinfectants (bactericides) and preservatives which are highly safe and effective for living organisms is obviously important. These fields are enormous and diversified, and cannot be explained in a single word. However, antibacterial agents include pathogenic microorganisms (bacteria, fungi, viruses, etc.) that have propagated in vivo, surgical layers, wound sites, and the like. ) Is a preparation that acts bactericidally or bacteriostatically, and is also applied as a prophylactic agent for infection.

On the other hand, disinfectants are used for wound sites, medical tools such as surgical instruments, contact lenses, ophthalmology including conjunctival sac, dental for the oral cavity and throat, fingers and skin, obstetrics and gynecology and urology. It is widely used as a drug for killing pathogens or preventing infection. Preservatives (preservatives) are mixed in cleaning and preservatives for contact lenses, various pharmaceutical solutions including eye drops, quasi-drugs, food and drinking water, cosmetics, and household and industrial detergents. It is used as an additive for preventing germs, molds and the like from propagating bactericidal or bacteriostatic. As described above, antibacterial agents, disinfectants, and preservatives are diversified, but technical development has been made according to the purpose, effect, application, etc. of each field.

For cleaning and preserving solutions for contact lenses
Preservatives used include sorbic acid and boric acid-borax
There is. These have relatively low bactericidal activity (bacteriostatic
Use), often the propagation of microorganisms, and contamination in the container
To be observed. In addition, benzalco chloride has a strong bactericidal effect
Ium, chlorobutanol, chlorhexidigluconate
And parahydroxybenzoic acid esters
Soft contact lenses and tact lenses
And storage on oxygen and oxygen permeable hard contact lenses
Product phenomenon occurs, resulting in lens deformation, deterioration and
Corners generated by the sustained release of accumulated preservatives from the lens
Difficult to use the above preservatives due to conjunctival disorders
(Japanese Patent Publication No. 8-16042 and Nikkore magazine34
(4), pp. 267-276, 1992).

[0005] Chemical disinfectants included in multipurpose care formulations for contact lenses include polyhexamethylene biguanide,
Chlorhexidine and polyquaternium are used. However, when higher concentrations of these disinfectants are used due to emphasis on bactericidal properties, cell damage and corneal coloring may occur. On the other hand, if a disinfectant is used at a lower concentration in order to suppress these obstacles, the antibacterial activity is reduced, so that there is still a considerable problem in the complexity of prescribing the disinfectant (Japanese Patent Publication No. 6-49642). Reference). In addition, some disinfectants of 3% hydrogen peroxide have a low bactericidal effect depending on the type of microorganism, and may cause corneal damage if misused.

[0006] Various pharmaceutical liquids including eye drops using reusable containers include preservatives such as benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, paraoxybenzoates, sorbic acid, chlorobutanol and thimerosal. Has been used as an agent. However, cationic surfactants such as benzalkonium chloride, benzethonium chloride and chlorhexidine gluconate, p-hydroxybenzoates and chlorobutanol have strong antibacterial activity, but eye drops containing these substances are frequently applied. It is said that preservatives greatly affect preservatives and cause corneal disorders for people with abnormal tear kinetics such as corneal scars or dry eye symptoms (Ophthalmology 3)
1 , pages 43-48, 1989 and Ophthalmology 33 , 533.
538 pages, 1991). Sorbic acid has a small preservative effect as described above, and thimerosal is a mercury compound, so its use is not currently recognized in Japan.

Disinfectants used as eye drops include benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, and alkylpolyaminoethylglycine. These are used for washing and disinfecting the conjunctival sac, and have side effects such as eye irritation, shock, rash, and itching. For dental use, azulene is used as a mouthwash for disinfecting the oral cavity and throat and preventing infection of tooth extraction wounds.
Disinfectants such as povidone-iodine, the cationic surfactants domiphen bromide and benzethonium chloride have been used.

[0008]

SUMMARY OF THE INVENTION An object of the present invention is to provide a use of a composition for controlling harmful microorganisms for disinfection and preservation. Another object of the present invention is to provide a use of a composition excellent in biosafety and excellent in disinfecting and preservative effects for disinfecting and preserving. Still another object of the present invention is to provide a preservative and a chemical disinfectant for cleaning and preserving a contact lens of the above composition, and also a preservative and disinfectant for various pharmaceutical preparations including eye drops and dental agents. To provide use as.

[0009]

Means for Solving the Problems The present inventors have conducted intensive studies in order to solve the above-mentioned problems, and as a result, a surfactant which does not exhibit its disinfecting / preserving effect alone or has a weak effect, The aqueous solution in which at least three components of a non-reducing saccharide or a polyol and a chelating agent coexist is surprisingly capable of exhibiting a strong disinfecting and preservative effect, and accordingly, a formulation applicable to various industrial fields. Was prepared, and the present invention was completed.

That is, according to the present invention, the above objects and advantages of the present invention are as follows: (A) a surfactant, (B) a non-reducing saccharide or polyol, and (C) a chelating agent. Use of the composition for controlling harmful microorganisms for disinfection and / or preservation is provided. Each component of the present invention is widely used in various fields and is also guaranteed biosafety. The use of these three components in a disinfectant / preservative based on a composition of these three components has been unknown at present. Therefore, if the biosafety of each preparation according to the purpose of use is confirmed, it can be a revolutionary disinfection and preservative system that can be used in various fields.

(A) used in the composition of the present invention
As the surfactant, at least one selected from cationic, anionic, amphoteric and nonionic compounds can be used according to the purpose of use and the target industrial field.

As the cationic surfactant, at least one selected from alkylamine salts, alkylammonium salts and the like can be used. Examples of the alkylamine salt include N-coconut fatty acid acyl-L-arginine ethyl.DL
-Pyrrolidone carboxylate.

Examples of the anionic surfactant include alkyl benzene sulfonic acid, alkyl sulfuric acid, α-olefin sulfonic acid, polyoxyethylene alkyl ether sulfate, alkyloyl methyl taurine, alkyloyl benzalcosin, N-acyl sarcosine, polyoxyl From the group of ethylene alkyl ether phosphoric acid, polyoxyethylene alkyl phenyl ether sulfate, hydrogenated coconut oil fatty acid glyceryl sulfate, carboxylated polyoxyethylene lauryl ether or their sodium, potassium and triethanolamine salts and methyl taurine derivatives and their salts At least one selected one can be used.

As the zwitterionic surfactant, for example, N
-Lauroylaminopropyl-N, N-dimethylglycine, N-cocoylaminopropyl-N, N-dimethylglycine, N-lauroylaminopropyl-N-carboxymethyl-N-hydroxyethylglycine, N-oleylaminopropyl-N- Carboxymethyl-N-hydroxyethylglycine, N-3-dodecyloxy-2-hydroxypropyl-N, N-dimethylglycine, N-cocoylaminopropyl-N-hydroxyethyl-3-aminopropionic acid, tri [3- (N -Cocoylaminoethyl-N-hydroxyethyl-N-carboxymethyl) amino-2-hydroxypropanol] phosphate, alkyldiaminoethylglycine hydrochloride (the alkyl group is mainly composed of those containing 12 and 14 carbon atoms) Etc.) It can be used at least one member selected from these groups.

Examples of the nonionic surfactant include poly (oxyethylene) -poly (oxypropylene) block copolymer (poloxamer), polyoxyethylene alkyl ether, polyoxyethylene alkylphenyl ether, polyoxyethylene alkyl ester, and polyoxyethylene alkyl ester. Oxyethylene sorbitan alkyl ester, polyoxyethylene hydrogenated castor oil, fatty acid monoglyceride, propylene glycol fatty acid ester, fatty acid sucrose ester and poly (oxyethylene) -poly (oxypropylene)
Ethylenediamine condensate (poloxamine) and the like can be used alone or in combination of two or more.
The above surfactant is used in an amount of 0.00000 of the total amount of the preparation of the present invention.
It is used in a concentration range of 5 to 1.0% by weight.

(B) Non-reducing saccharides include 1-O
-Alkyl glucose, sucrose, trehalose, mannitol, maltitol, xylitol, erythritol, arabitol, ribitol, threitol, darcit, sorbitol, dulcitol, raffinose, gentianose, melezitose, planteose, stachyose, verbascose, and the like. They can be used alone or in combination of two or more. Also,
Polyols include ethylene glycol, glycerin, propylene glycol, polyvinyl alcohol and polyethylene glycol or mixtures thereof. These non-reducing saccharides or polyols are used in a concentration range of 0.01 to 10.0% by weight of the whole preparation.

As the chelating agent (C), ethylenediaminetetraacetic acid, gluconic acid, citric acid, tartaric acid, diethylenetriaminepentaacetic acid and their sodium and potassium salts, sodium polyphosphate and sodium nitrilotriacetate are preferred. Disodium tetraacetate is particularly preferred. These chelating agents are used in a concentration range of 0.01 to 1.0% by weight of the whole preparation.

The composition for controlling harmful microorganisms in the present invention is obtained by dissolving the above-mentioned (A) surfactant, (B) non-reducing saccharide or polyol and (C) chelating agent in an aqueous medium. Prepared. As an aqueous medium,
An aqueous solution in which an isotonic agent and / or a buffer or a hydrophilicity-imparting agent is dissolved in purified water is preferably used. The tonicity agent, buffering agent or hydrophilicity-imparting agent is preferably prepared by dissolving each in 2% by weight or less in purified water. As tonicity agents, sodium chloride and potassium chloride are preferred. Examples of the buffer include phosphate buffers such as sodium dihydrogen phosphate and disodium monohydrogen phosphate;
Preferred are boric acid buffers such as borax and boric acid, and tris buffers such as trishydroxymethylaminomethane (tromethamine), dilute hydrochloric acid and trismalate and dilute caustic soda solution. As the hydrophilicity-imparting agent, polyvinylpyrrolidone, polyvinyl alcohol, sodium hyaluronate, hydroxypropylmethylcellulose, carboxymethylcellulose, hydroxyethylcellulose, glycerin, propylene glycol, dextran, and polyquaterniums are preferable.

The composition of the present invention was subjected to a preservative efficacy test of the composition for controlling harmful microorganisms, and as a result, a surfactant,
The three main component-containing preparations of a non-reducing saccharide or polyol and a chelating agent showed a strong preservative effect. However, the preparation lacking at least one of the three main components and the preparation containing only the main component had no or weak preservative effect. Although the antimicrobial mechanism of the composition of the present invention is not known at present, the role of the non-reducing saccharide or polyol in the antimicrobial system is particularly interesting, and it will be left as a future research subject. Have been.

According to the composition of the present invention, with respect to biosafety, anionic and nonionic surfactants among the surfactants used in the preparation have already been used in the washing / preserving solution for contact lenses. It has also been used in various pharmaceutical preparations, quasi-drugs and cosmetics, including eye drops and dental agents, and some of the aforementioned nonionic surfactants have been approved for use as food additives. Safety has been confirmed. Similarly, disodium ethylenediaminetetraacetate, which is a chelating agent, is used as a washing / preserving solution for contact lenses, a disinfecting solution thereof, and a stabilizer for various pharmaceuticals and cosmetics. It is also used as an antioxidant in canned and soft drinks as a food additive.

Among the non-reducing saccharides or polyols,
In particular, mention may be made of trehalose, mannitol and glycerin which most strongly express the antibacterial activity of the system of the invention. Trehalose is metabolized to carbon dioxide in an intravenous test in rabbits (Biochem. Physiol., 50B ,
221, p.221, 1975), there is a possibility of using an infusion solution to humans, and there is no problem in the biosafety of a fat-containing nutritional composition and an amino acid-containing nutritional composition of an infusion component containing the substance. (Japanese Unexamined Patent Publication No. 6-199664)
And Japanese Patent Application Laid-Open No. 6-70718) and its use in foods (see Japanese Patent Application Laid-Open No. 6-170221). In addition, mannitol and glycerin are listed in the Japanese Pharmacopoeia as an injection solution and an additive thereof, and have a track record of use. Therefore, trehalose, mannitol and glycerin are both highly biosafe substances.

As described above, the three main components of the surfactant, non-reducing saccharide or polyol, and chelating agent used in the composition of the present invention have been used and the biosafety has been confirmed. Has been
The composition of the present invention can be used as a preservative and a chemical disinfectant for cleaning and preserving solutions for contact lenses, and as a preservative and a disinfectant for cosmetics and pharmaceutical preparations including eye drops and dental agents. .

[0023]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto. Example 1 Solutions No. 1 to No. 7 shown in Table 1 were prepared.

[0024]

[Table 1]

The solution is prepared by dissolving hydroxyethyl cellulose in about 80% distilled water and then dissolving anhydrous disodium phosphate and anhydrous monosodium phosphate. Thereafter, disodium ethylenediaminetetraacetate, trehalose, and glycerin are dissolved. Finally, sodium α-olefin sulfonate is dissolved, and the volume is adjusted to a predetermined volume with distilled water (pH of the aqueous solution is 7.2). E. col (E. col)
i), P. aeruginos
a), S. aureus and C. albicans are added at about 10 ⁶ to 10 ⁸ per ml, and the mixture is allowed to stand at 25 ° C. After 3 days and 7 days, 1 ml of each of the solutions inoculated with the bacteria is mixed with an agar medium (Tables 3 and 4), cultured in a plastic dish, and the number of viable bacteria is measured. Table 2 shows the results.

[0026]

[Table 2]

Sodium α-olefin sulfonate as a surfactant, trehalose as a non-reducing saccharide or /
No. 4, 5 and 6 containing glycerin and disodium ethylenediaminetetraacetate as a chelating agent
Shows the preservative efficacy, but the solution No. 1, 2, 3 which does not contain any one, and the solution No. which does not contain any of sodium α-olefin sulfonate, trehalose or / and glycerin, and disodium ethylenediaminetetraacetate .7 had little or no preservative effect on all test microorganisms.

[0028]

[Table 3]

[0029]

[Table 4]

Example 2 Solutions No. 8 to No. 11 shown in Table 5 were prepared.

[0031]

[Table 5]

A solution can be prepared by dissolving a hydrophilicity-imparting agent, a buffer, a chelating agent, a tonicity agent, a non-reducing saccharide, and a surfactant in the same order as in Example 1 (the pH of the aqueous solution is 7.2). In the same manner as in Example 1, e.
E. coli and C. albicans (Ca)
Ibicans), and the number of viable cells was measured 3 days and 7 days later. Table 6 shows the results.

[0033]

[Table 6]

Example 3 Solutions No. 12 to No. 15 shown in Table 7 were prepared.

[0035]

[Table 7]

A solution can be prepared by dissolving a hydrophilicity-imparting agent, a buffer, a chelating agent, a tonicity agent, a polyol, and a surfactant in the same order as in Example 1 (pH of the aqueous solution is 7.2). ). In the same manner as in Example 1, e.
E. coli and C. albicans (Ca)
Ibicans), and the number of viable cells was measured 3 days and 7 days later. Table 8 shows the results.

[0037]

[Table 8]

Tables 2, 6 and 8 of Examples 1, 2 and 3
Considering the results of the above, it was confirmed that sufficient preservative efficacy was exhibited even when various non-reducing saccharides or polyols, anionic surfactants and nonionic surfactants were used.

Example 4 No. 16 to No. 17 solutions shown in Table 9 were prepared.

[0040]

[Table 9]

A solution can be prepared by dissolving a hydrophilicity-imparting agent, a buffer, a chelating agent, a tonicity agent, a non-reducing saccharide, and a surfactant in this order as in Example 1 (the pH of the aqueous solution is 8.0). In the same manner as in Example 1, e.
E. coli and C. albicans (Ca)
lbicans), and the number of viable bacteria was measured 3 days later. Table 10 shows the results.

[0042]

[Table 10]

From the results in Table 10, it was confirmed that the storage effect was exhibited even when the buffer was changed. Also, the addition of non-reducing saccharides enhanced the preservative efficacy.

Example 5 Solutions No. 18 to No. 21 shown in Table 11 were prepared.

[0045]

[Table 11]

A solution can be prepared by dissolving a hydrophilicity-imparting agent, a buffer, a chelating agent, a tonicity agent, a non-reducing saccharide or a polyol, and a surfactant in this order as in Example 1. pH 7.2). E. coli and P. aeruginosa (P. aeru) were added to the solutions in Table 11.
ginosa), S. aureus (S. aureu)
s) and C. albicans
s) was inoculated at about 10 ⁶ to 10 ⁸ per ml, and the number of viable cells up to 6 hours was measured. Table 12 shows the results.

[0047]

[Table 12]

The results in Table 12 show that the blended preparation of trehalose or glycerin which is a non-reducing sugar, sodium α-olefin sulfonate which is a surfactant, and disodium ethylenediaminetetraacetate which is a chelating agent is as follows. It showed that it also exerted a sufficient disinfection effect.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Shingo Hishiya 156-5 Kamimidai, Toyooka, Hyogo Prefecture Inside of FTEX Research Institute Co., Ltd. (72) Inventor Fumio Saito 156-5 Kamimidai, Toyooka City, Hyogo Prefecture Inside the Futex Research Institute (72) Inventor Takashi Fujii 156-5 Kamimidai, Toyooka City, Hyogo Prefecture

Claims (5)

[Claims] 1. Use of a composition for controlling harmful microorganisms containing (A) a surfactant, (B) a non-reducing saccharide or polyol and (C) a chelating agent for disinfection and / or preservation. 2. The use according to claim 1, wherein the surfactant is at least one selected from the group consisting of cationic, anionic, zwitterionic and nonionic compounds. 3. The non-reducing carbohydrate is 1-O-alkylglucose, sucrose, trehalose, mannitol, maltitol, xylitol, erythritol, arabitol, ribitol, threitol, darcit,
The use according to claim 1, which is at least one selected from the group consisting of sorbitol, dulcitol, raffinose, gentianose, melezitose, planteose, stachyose and verbascose. 4. The use according to claim 1, wherein the non-reducing polyol is at least one selected from the group consisting of ethylene glycol, glycerin, propylene glycol, polyvinyl alcohol and polyethylene glycol. 5. The chelating agent comprises ethylenediaminetetraacetic acid, gluconic acid, citric acid, tartaric acid, diethylenetriaminepentaacetic acid and the sodium salts of these acids and the potassium salts of these acids, sodium polyphosphate and sodium nitrilotriacetate. Claim 1 selected from the group
Use of the description.